Clinical Variability of Family Members with the C104R Mutation in Transmembrane Activator and Calcium Modulator and Cyclophilin Ligand Interactor (TACI)

Abstract

The C104R mutation does not correlate with the clinical phenotypes in this family.

New diagnostic criteria for common variable immune deficiency (CVID), which may assist with decisions to treat with intravenous or subcutaneous immunoglobulin

“…Mutations of these genes have been identified in healthy people, albeit at a lower frequency than symptomatic individuals [11,12]. We and others have shown that C104R mutations of the TACI gene do not segregate as expected with symptomatic family members [13]. Current thought is that these genes predispose to CVID rather than cause it.…”

“…In clinical practice, patients with slightly reduced IgG levels would rarely be investigated, particularly if they are symptomatically well. Impaired vaccine response is the second and most contentious criterion [13]. The ESID/PAGID diagnostic criteria do not specify which vaccines should be used [13].…”

“…Impaired vaccine response is the second and most contentious criterion [13]. The ESID/PAGID diagnostic criteria do not specify which vaccines should be used [13]. Vaccine responses in CVID have been reviewed recently by an expert panel of the American Academy of Asthma Allergy and Immunology (AAAAI) [23].…”

TACI deficiency enhances antibody avidity and clearance of an intestinal pathogen

“…Other variants that impair signaling by TACI are also found, albeit at lower frequencies, in normal individuals (20). Still more curious, individuals homozygous for C104R exhibit a milder phenotype of CVID and are less likely to develop autoimmunity than are individuals heterozygous for C104R (14,18,21), and some respond normally to vaccination despite having hypogammaglobulinemia (22). The vast range of manifestations associated with TACI variants in human subjects, from normal to severe CVID, and the reciprocal impact of gene dosage on the severity of the disease suggest that either background genes exert more impact on phenotype than any TACI allele, or the high prevalence of TACI variants is adaptive in response to environmental factors, or both.…”

Primary immunodeficiency: common variable immunodeficiency

“…Мутации этих генов были идентифицированы у здоровых людей [22,23,24]. Существует теория о том, что у «здоровых» людей могут обнаруживаться эти гены, однако, первые клинические признаки ОВИН начнут проявляться в старческом возрасте (плечо генов) [13].…”